International Agency for Research on Cancer (IARC) - Summaries & Evaluations


VOL.: 26 (1981) (p. 165)

5. Summary of Data Reported and Evaluation

5.1 Experimental data

Cyclophosphamide is carcinogenic in rats after its oral or intravenous administration, producing benign and malignant tumours at various sites, including the bladder. It is carcinogenic in mice following its subcutaneous injection, producing benign and malignant tumours at the site of injection and at distant sites. There was some evidence of its oncogenicity in mice and rats following intraperitoneal injection. The combined administration of cyclophosphamide intraperitoneally and of 2-naphthylamine orally to mice resulted in the induction of carcinomas of the bladder at doses of the compounds which, given individually, did not produce bladder cancer.

The teratogenic effects of cyclophosphamide are well established in many animal species. The drug can also be embryolethal at doses nontoxic to the mother.

Cyclophosphamide demonstrated mutagenic activity in several different assays (bacteria, yeast and mammalian cells in vitro, and Drosophila and mice in vivo). The agent also induced chromosomal aberrations in mammalian cells of several species in vitro and in vivo. Moreover, it induced morphological transformation of mammalian cells in vitro.

5.2 Human data

Cyclophosphamide has been widely used since the early 1950s in the treatment of malignant lymphoma, multiple myeloma, and cancers of the breast, ovary and lung. It has also been used in the treatment of certain chronic diseases, such as rheumatoid arthritis and chronic glomerulonephritis and other nonmalignant diseases.

Although two cases of limb reduction defects have been reported among the offspring of women treated with cyclophosphamide during pregnancy, no epidemiological data were available to the Working Group for assessing the embryotoxic risk to man. Increases in chromosomal aberrations and sister chromatid exchanges were seen in peripheral blood lymphocytes of patients treated with cyclophosphamide.

There is epidemiological evidence that cyclophosphamide increases the incidence of bladder cancer, and there is a suggestion that the incidence of other cancers may also be increased. There are also many case reports of cancer, particularly bladder cancer and acute nonlymphocytic leukaemia, following cyclophosphamide therapy.

5.3 Evaluation

There is sufficient evidence for the carcinogenicity of cyclophosphamide in mice and rats. There is sufficient evidence that cyclophosphamide is carcinogenic in humans.

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Vol. 9 (1987)

Subsequent evaluation: Suppl. 7 (1987)

Last updated: 8 April 1998

    See Also:
       Toxicological Abbreviations
       Cyclophosphamide (ICSC)
       Cyclophosphamide  (IARC Summary & Evaluation, Supplement7, 1987)
       Cyclophosphamide (IARC Summary & Evaluation, Volume 9, 1975)